In the aging modern society, osteoarthritis (hereinafter, referred to as OA), which is joint pain and functional disorder attributable to joint degeneration, is the most common joint disease throughout the world, and is one of the leading causes of disability in daily life of the elderly.
Currently, OA treatments include, for example, treatment by oral administration of analgesic drug such as non-steroidal anti-inflammatory drug, which is broadly used for various pains, and a treatment by intra-articular administration of hyaluronic acid solution.
The former treatment is a symptomatic therapy for relieving joint pain with use of a synthetic medicine having sharp analgesic effects.
On the other hand, the latter treatment is a therapy for treating joint disease, which is impaired joint function attributable to reduction of the joint fluid and degeneration of joint cartilage, by lubricant action, shock absorber action, cartilage metabolism improvement action and joint pain relieving action, which are possessed by the hyaluronic acid.
Hereinafter, hyaluronic acid or a derivative group therefrom may be referred to as HA.
Currently, intra-articular formulations using hyaluronic acid and derivative thereof (hereinafter, referred to as the IA-HA product.) are commercially available as products formed from solution of sodium hyaluronate, and products formed from solution of a cross-linked hyaluronic acid derivative. Examples of the IA-HA products formed from solution of sodium hyaluronate include ARTZ (registered trademark), SYNVISC (registered trademark), HYALGAN (registered trademark) and ORTHOVISC (registered trademark). Examples of the IA-HA product formed from solution of a cross-linked hyaluronic acid derivative include SYNVISC (registered trademark) and DUROLANE (registered trademark). SYNVISC (registered trademark) is composed of a hyaluronic acid derivative cross-linked with a covalent bond by a small amount of aldehyde, and a hyaluronic acid derivative made by further cross-linking the derivative by divinyl sulfone. DUROLANE (registered trademark) is an epoxy cross-linked joint protective agent (see U.S. Patent Application Publication No. 2006/0148755).
These IA-HA products are administered basically every 1 to 2 weeks to obtain desired therapeutic effects (see “The Journal of Rheumatology” 2004, 31: 4, pp. 775-782; and “Current Medical Research and Opinion” 11; 205-213, 1988). Since hyaluronic acid has viscoelasticity, intra-articular administration of these IA-HA products is performed with use of a thicker injection needle than that for usual injections. Therefore, the intra-articular administration of these IA-HA products gives the feels of more invasion and boring pain than administration of usual injections, and the administration of these IA-HA products in the single treatment period is limited to 5 times in principle in Japan. However, conventional products require continuous administrations every week, which may become a great burden to patients who reside at a distant place from the hospital or who have difficulty in visiting weekly owing to the job of the patients. Accordingly, products requiring administrations at fewer frequencies and showing equivalent or better therapeutic effects to or than those of the conventional IA-HA products are sought.
Recently, there has been reported a product (SYNVISC-ONE (trademark)) that is a new regimen using SYNVISC (registered trademark) and allows a single injection with increased dosage up to three times a usual dosage (2 mL) of conventional products. According to the report, it is believed such that the therapeutic effects last for 26 weeks after a single administration (see “ARD Online First,” published on Mar. 19, 2009 as 10. 1136/ard. 2008, 094623). However, such therapeutic effects are only results from the single administration with three-time dose (6 mL) of the conventional product. Further, there is also a demerit that a burden to patients is increased by triple dose intra-articular injection at one shot compared to the conventional product.
In addition, International Publication Pamphlet No. WO 2008/069348 reports a therapeutic agent for a joint disease for intra-articular administration by a photo cross-linked hyaluronic acid derivative, which is a different cross-linked form from that of the commercially available cross-linked hyaluronic acids, and has durable effects with a single administration. However, there is no specific disclosure or suggestion regarding the ultralong-term durability in human OA treatment.
In addition, IA-HA products are focused on long term enhancement of patient's QOL by improving comprehensive joint functions, and hardly expected to have rapid-acting analgesic effects as expected in, for example, non-steroidal anti-inflammatory analgesic drugs (see “The Journal of Rheumatology” 2004, 31: 4, pp. 775-782; “OsteoArthritis and Cartilage” (2004) 12, 642-649; “ARD Online First,” published on Mar. 19, 2009 as 10. 1136/ard. 2008. 094623; “Arthritis & Rheumatism,” Vol. 43, No. 9, pp. 1905-1915 (2000)).
As described above, a number of IA-HA products exist, but there has been no report of an intra-articular formulation that shows equivalent or better effects with a single administration to or than the effects shown with multiple administrations of any of conventional IA-HA products, without an increase of the single dosage, and for a long period, particularly more than a half year from the viewpoint of invasion.
Consequently, desired are products that can have early onset of prominent analgesic effects, with a lower frequency of administration and a smaller dosage of a single administration as possible, and show equivalent or better therapeutic effects to or than conventional IA-HA products.